European Thyroid Journal最新文献

Introduction: Insulin resistance (IR) is a phenomenon commonly observed in pregnancy. Increased insulin concentrations might impact thyroid function and structure during gestation.

Objectives: This study investigates the bidirectional relationship between IR indices and thyroid function and morphology in pregnant women.

Methods: In 1,069 gravid participants of the Polish National Programme for Elimination of Iodine Deficiency (2007-2017), blood samples were analyzed for thyroid-stimulating hormone (TSH), FT3, FT4, aTPO, fasting glucose and insulin concentrations, and the thyroid structure was assessed with ultrasound (in 1,065 subjects). Based on calculated homeostatic model assessment of insulin resistance (HOMA-IR) values, participants were stratified into two subgroups: HOMA-nl (HOMA-IR <2.5) and HOMA-h (HOMA-IR ≥2.5), comprising 894 and 175 women, respectively.

Results: Significant difference in mean TSH (1.77 ± 1.17 vs 1.96 ± 1.04; P = 0.008) and mean FT4 (12.65 ± 2.3 vs 11.47 ± 1.9; P = 0.001) concentrations between HOMA-nl and HOMA-h groups was found. The subgroups did not differ in thyroid nodularity or multinodular goiter prevalence. HOMA-IR positively correlated with TSH concentrations, BMI and thyroid volume. Serum FT3 and FT4 concentrations showed negative correlations with HOMA-IR.

Conclusions: IR seems to affect the thyroid function of gravid women by diminishing the ability to respond to increased thyroid hormone demand. Thyroid volume increase during pregnancy may be influenced by IR; however, its short-term effect on thyroid nodularity appears to be negligible.

Objective: The optimal treatment with antithyroid drugs (ATD) for a first episode of Graves' disease (GD) remains controversial. Methods Retrospective, two academic centres study of newly diagnosed GD between 1990 and 2022, treated with ATD in block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. Sixty patients received high-dose B+R (HD) with fixed ATD dose maintained during the study, and sixty patients low-dose B+R (LD) with lower ATD dose adjusted during the study. Results Baseline characteristics were similar in both groups. The point-prevalence of euthyroidism was not different between HD and LD (38% vs 47%, p=0.460 at 6 months, 69% vs. 82%, p=0.194 at 12 months, 70% vs. 78%, p=0.370 at 18 months, respectively). At 18 months, 27% HD vs. 38% LD (p=0.242) had thyroid eye disease. There were no differences in the number or type of ATD-related adverse events (AE) ( no AE 73% vs. 78%, p=0.707). LD received mean lower ATD dose (15.3 ± 4.2 vs. 30.0 ± 0.0 mg/day, p<0.001) and lower levothyroxine dose (72.6 ± 16.7 vs. 100.6 ± 24.5 µg/day, p<0.001). After a first course of ATD, 63% of HD patients and 60% of LD patients relapsed (p=0.707), after a median time [interquartile range] of 11.0 [18] vs. 7.0 [19] months (p=0.109) Conclusion We observed similar relapse rates in patients with a first episode of GD receiving up to 50% less ATD and 30% less levothyroxine dose than high-dose B+R regimen.

Objective: Maternal thyroid peroxidase antibody (TPOAb) positivity has been associated with a variety of pregnancy complications and has potential neuropsychological developmental implications for the offspring. The aim of our study was to explore the effect of maternal TPOAb levels on emotional and behavioural problems in children.

Design: Cohort study Participants: Based on the Maanshan Birth Cohort in China, 2464 mother-infant pairs were included in this study.

Measurements:  Repeated blood samples were collected from pregnant women and TPOAb and FT4 were measured retrospectively by electrochemiluminescence immunoassay (ECLIA). The Strengths and Difficulties Questionnaire (SDQ) was used to assess the emotional and behavioural problems of 4-year-old preschoolers.

Results: After adjusting for potential confounders, maternal TPOAb positivity during the third trimester of pregnancy was found to be associated with an elevated risk of conduct problems in girls, with an OR of 2.190 (95% CI: 1.137 - 4.219). Conversely, maternal TPOAb positivity in the first trimester was linked to a decreased incidence of prosocial behavior in boys, with an OR of 0.451 (95% CI: 0.237 - 0.861).

Conclusions: Maternal TPOAb positivity during pregnancy may be associated with emotional and behavioral problems in preschool - aged children.

Introduction: little is known about sex differences in lenvatinib treatment safety and efficacy.

Methods: real-word retrospective Italian multicenter study enrolling patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib.

Results: 138 patients (64 females) were included, with a median follow-up of 26 months (2-72). More men performed physical activities (34%vs17%, p=0.024). The frequency of smoking and alcohol consumption was higher in men (58%vs33%, p=0.003; 45%vs17%, p=0.001). We did not find sex differences in lenvatinib dose reduction due to adverse events, AE (78% of females vs 85% of males). 99% of patients developed at least one AE, with no sex difference in their number and the time to first AE. Severe AEs occurred in 74% of males and 66% of females (p=0.398), with a mean dose of 18.2 mg (±5.7), and a median time at the first severe AE of 9 weeks (1-154). Stomatitis/mucositis and hematological disorders were more frequent in females (48%vs30%, p=0.016; 17%vs4%, p=0.011). Gastrointestinal disorders were higher in males (15%vs2%, p=0.010). Eighty-seven patients interrupted lenvatinib due to AEs (median time: 3 months (0-48), mean dose: 17 mg ±5.5). Discontinuation occurred in 21 patients, 5 for severe AEs. No sex differences were found in progression-free survival, overall survival and disease control rate. Liver metastases were associated with disease progression (HR 3.73, 95%CI 1.06-13.12, p= 0.040) or death (HR 4.82, 95%CI 1.75-13.25, p= 0.002) only in females.

Conclusions: lenvatinib is effective in both sexes and exhibits a good safety profile, with a sex difference in the frequencies of some adverse events.

Objective: Mammalian acid chitinase (AMCase; CHIA) has potential as a biomarker and drug target in the fields of medicine and pharmacology, and its role in inhibiting tumor growth and Th2 cell-mediated asthma-related inflammation has become a research hotspot. However, the role of CHIA in thyroid cancer is unclear.

Methods: Tissue microarrays and thyroid cancer cell lines were used to detect CHIA expression and determine its clinical relevance. CHIA gene expression was altered in thyroid cancer cells to examine the effects of CHIA expression on the biological behavior of thyroid cancer cells, and the related molecular mechanisms involved were explored.

Results: We first examined CHIA expression in a thyroid tissue microarray using immunohistochemistry. We found that CHIA was significantly upregulated in thyroid cancer tissues relative to paired thyroid cancer adjacent tissues. After correlation analysis, we found that upregulated CHIA expression correlated with the TNM stage of patients with thyroid cancer. Similarly, CHIA expression was significantly higher in the thyroid cancer cell lines BCPAP, TPC-1, KTC-1, and FTC133 than in the human normal thyroid epithelial cell line Nthori-3-1. CHIA promotes proliferation, migration and invasion; inhibits thyroid cancer cell apoptosis; and regulates markers of proliferation and EMT. Mechanistically, CHIA activated the JAK2/STAT3 signaling pathway in thyroid cancer cells.

Conclusions: CHIA upregulation promoted the proliferation, migration and invasion of thyroid cancer cells through JAK2/STAT3 signaling pathway activation. Therefore, CHIA could represent a potential new oncogene for patients with thyroid cancer.

Background UK guidance on the assessment and management of thyroid disease was set out in NICE guideline NG145 in 2019 and is expected to result in an increase in radioactive iodine (RAI) being offered as a first-line definitive treatment for hyperthyroidism. Methodology In this work we analyse longitudinal UK Biobank data to assess all-cause mortality and comorbidity risks associated with the main treatment modalities for 793 participants with hyperthyroidism, specifically antithyroid drugs (ATDs), RAI and thyroidectomy. Results Participants treated with RAI showed reduced all-cause mortality compared with those treated with ATD alone (time to event ratio 1.8, 95% CI 0.9 - 3.6), albeit the result did not reach statistical significance, as did those treated by thyroidectomy (time ratio 2.0, 95% CI 1.1 - 3.9). For treated patients odds ratios were generally elevated for osteoporosis, cardiovascular events and atrial fibrillation, but again did not reach statistical significance except for those patients treated by ATDs with an odds ratio for atrial fibrillation of 2.2 (95% CI 1.2 - 4.1) versus controls. Conclusion Our findings were consistent with those previously reported in the literature, and do not reveal any evidence from the UK Biobank to contradict the safety of RAI being offered as a first-line treatment. The data are also suggestive, however, that treatments do not fully eliminate risks of complications related to hyperthyroidism. This reinforces the need for both clear communication where there may be risks of complications such as osteoporosis, as well as clinical support for patients, even after definitive treatment.

Background: Management of benign nodular thyroid disease (BNTD) has changed dramatically over the past two decades, as reflected by international guideline recommendations.

Purpose: We sought to document the preferences regarding the management of euthyroid BNTD among thyroid-dedicated members of the Spanish Society of Endocrinology and Nutrition (SEEN) and assess the extent to which present international guideline recommendations have been incorporated into ordinary practice.

Methods: An online survey on the management of a standard case of BNTD among SEEN thyroid experts and exploration of variations in management following different clinical scenarios, in which variables such as sex, age, ultrasound characteristics, fine needle aspiration results or patient preferences change.

Results: Two hundred and eleven (9% SEEN members) participated in the survey. Most of them, 147 (69.7%), recommended periodic monitoring, 43 (20.3%) surgery and 21 (10.0%) minimally invasive procedures (MIP). No participant opted for levothyroxine or radioiodine. Management of BNTD was modified based on patient preferences, both in favour of more aggressive (surgery) and more conservative (MIP or monitoring) options.

Conclusions: The vast majority of Spanish thyroidologists followed the international guideline recommendations for BNTD management. The trend shows the positive impact of the guideline recommendations with a shift towards more conservative management, taking into account patient preference as a binding element in therapeutic decision-making.

Primary congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, and may be etiologically subdivided into thyroid dysgenesis, referring to abnormal thyroid development, and dyshormonogenesis, where a defective thyroid hormone biosynthesis pathway results in inadequate hormone production despite a structurally intact gland. Delayed treatment of neonatal hypothyroidism may result in irreversible neurodevelopmental impairment; therefore, where available, CH screening programs facilitate prompt diagnosis. However, the molecular basis for CH remains unclear in most of the cases. This review summarizes current understanding of the genetic etiologies underlying primary CH and associated phenotypes. Classical genetic causes are discussed in the context of their role in normal thyroid physiology. Genes recently reported to play a role in the pathogenesis of CH are discussed, and novel genomic mechanisms in CH are described.

Metastatic differentiated thyroid cancer (DTC) is responsible for most thyroid cancer-related deaths, with an even worse prognosis for patients with radioactive iodine (RAI)-refractory DTC (RAIR-DTC). While multikinase inhibitors (MKIs) and tyrosine kinase inhibitors (TKIs) offer effective treatments for RAIR-DTC, most patients remain noncurative and eventually experience disease progression. In addition, long-term use of these medications is hindered by adverse events, drug resistance and high cost. Recently, the use of MKIs and TKIs has reignited interest in enhancing RAI incorporation. This approach aims to restore the effectiveness of RAI therapy in patients with RAIR-DTC by using agents that increase RAI uptake, potentially overcoming current treatment challenges. This review covers the molecular mechanisms behind RAI resistance, the definition of RAIR-DTC and the efforts to enhance RAI incorporation through various agents, including those currently undergoing clinical trials.

Background: This study aimed to investigate the changes in histological types and causes of death associated with thyroid carcinoma (TC) before and after the introduction of systemic drug therapy.

Methods: The records of 503 deceased patients treated for TC and with death from TC between January 2005 and June 2024 were reviewed in this retrospective cohort study. Multivariate logistic regression was applied to assess whether the number of patients with anaplastic TC (ATC) at diagnosis and the number of local-related deaths changed before and after the introduction of lenvatinib (i.e. 2005-2014 vs 2015-2024).

Results: Of the 503 patients, 157 (31%) had ATC, 253 (50%) had papillary TC (PTC), 67 (13%) had follicular TC (FTC), 17 (3%) had poorly differentiated TC, and nine (2%) had medullary TC. Respiratory insufficiency was the most common fatal condition, occurring in 192 cases (38%), followed by local-related death in 98 cases (19%) and brain-related conditions in 22 cases (4%). We found no difference in the frequency of patients with ATC at diagnosis (32 vs 30%; P-value = 0.772) and the frequency of local-related deaths (19 vs 20%; P-value = 0.736) between 2005-2014 and 2015-2024. These findings were supported by multivariate logistic regression models that adjusted for other covariates (adjusted P-value = 0.436 and 0.353, respectively).

Conclusions: ATC, including anaplastic transformation from PTC and FTC, still accounts for approximately 40% of thyroid cancer deaths after the introduction of systemic drug therapy. Respiratory insufficiency is the most common immediate cause of death.